There is very little information concerning basic pathogenetic mechanisms for the initiation of acute pancreatitis. Before more effective therapy can be devised, basic information concerning the pathogenesis of acute pancreatitis is needed. Many stimuli or clinical situations can initiate an episode of acute pancreatitis. Amongst the more common are alcohol, gall stones, drug administration, and ischemia. Utilizing an ex-vivo, isolated, perfused canine pancreas preparation, experimental models simulating these four clinical situations have been developed. By infusing free fatty acid into the arterial line of the isolated canine pancreas preparation, a model simulating alcoholic hyperlipemic pancreatitis has been produced. Gallstone pancreatitis can be simulated by partially obstructing the isolated pancreas ductal system and simultaneously stimulating the gland with secretin. Drug-induced pancreatic injury as produced by the administration of azathioprine markedly increased pancreatic secretion and decreased trypsin output in the isolated pancreas preparation. Finally, the effects of ischemia on the pancreas can be evaluated in the isolated canine pancreas preparation by decreasing the arterial p02, or by decreasing flow. By studying the early changes in these preparations, we hope to learn basic pathogenetic steps in the development of acute pancreatitis. This may lead to improve treatment of acute pancreatitis. Controlled clinical studies evaluating the efficacy of nasogastric suction and albumin administration in the treatment of acute pancreatitis will also be carried out.